1. Field of the Invention
This invention relates to the use of hydroxytetronic acid derivatives alone, or in combination with other ingredients such as unsubstituted hydroxytetronic acid, tetronic acid and/or tetronic acid derivatives, hydroquinone, glycolic acid, and/or ascorbyl palmitate, in compositions that whiten skin, and methods for using the compositions.
2. Description of Related Art
A variety of dermatological compositions have been suggested for skin whitening to improve the appearance of pigment disorders characterized by abnormal pigments such as that observed as postinflam-matory hyperpigmentation and other pigmented lesions, melasma, cafe au lait and liver spots spots, freckles and lesions observed in Addison's disease, hemochro-matosis, vitiligo, piebaldism, phenylketonuria, and the like, and/or for cosmetic purposes. Skin color is primarily determined by the amount of melanin present in epidermal cells, so many modern skin bleaching compositions either destroy melanin (typically by destroying or disrupting melanin granules) or inhibit its formation (often by inhibiting tyrosinase, a melanin biosynthetic enzyme, or melanocyte activity), or both. Many of these contain harsh chemicals such as peroxides, acids or formaldehyde, or thiolated materials such as glutathione, cysteine, mercaptosuccinic acid, mercaptodextran, and mercaptoethanol, which have an objectionable odor that makes products containing them undesirable to a consumer (discussed in U.S. Pat. No. 5,980,904 to Leverett and Dornoff, U.S. Pat. No. 5,747,006 to Dornoff, et al., and U.S. Pat. No. 6,077,503 to Dornoff; these and subsequent references are hereby incorporated herein in their entireties by reference).
Less stringent therapies have other disadvantages. The only treatment for hyperpigmentation that is approved in the United States for use by consumers without a prescription, for example, is the topical application of hydroquinone, which acts by suppressing melanocyte activity. Hydroquinone is oxidized by air, light, and tyrosinase itself, however, which adversely effects the shelf life of preparations containing it and its bioavailability upon application. Hydroquinone can cause burning, redness, sensitization and irritation in some persons, particularly after application of quantities sufficient to cause skin bleaching as it requires prolonged treatment before results are noticeable, and its oxidized products have been implicated in skin irritation and pigmentation rebound (U.S. Pat. No. 6,068,834 to Kvalnes, et al.). Topical retinoids and topical corticosteroids have been suggested as hypopigmenting agents, as have laser treatment and chemical peels, but these fall short of desirable responses. A new combination therapy recently suggested combines tretinoin and fluocinolone with hydroquinone (Willis, I., Skin & Aging Supp., Nov. 2000, 17–21). Kojic acid and arbutin have also been suggested, but these are marginal tyrosinase inhibitors and are not very bioavailable and thus have disappointing efficacy.
Other pleasanter compositions recently suggested employ natural materials, which have in some cases been used for centuries in Asia or Europe to bleach skin and skin areas, or enhance the appearance of fair skin. These include the use of lemon, orange, cucumber, ginko, carob, rose fruit, geraniuim herb, cinnamon, sweet marjoram, rosemary, clove, mulberry, licorice, bearberry, and acerola cherry extracts (ibid.). Boo, et al., suggested a furanone extracted from Pinaceae plants be used for whitening skin by inhibiting melanin formation (U.S. Pat. No. 5,602,259). The variability of active ingredients in these natural products sometimes limits their usefulness, particularly as skin type, color, age, and condition of vary greatly in different subjects, and make suggested dosages and regimens difficult to fashion. And other ingredients in the mixtures can cause allergic reactions in sensitive persons.
It would be desirable to have alternative preparations, and/or ones that improve the efficacy of presently known skin whitening agents.